Abstract The effects of repetitive heading in soccer, outside the purview of recognized concussion, are a topic of major public importance that has not been well defined. Recent work from our laboratory has shown that repetitive sub-concussive soccer heading is associated with evidence of microstructural tissue damage as well as cognitive impairments. We have found that there exists a threshold number of heads per year whereby subclinical and clinical impairments are evident. Despite this evidence of axonal and functional damage, we have not characterized individuals at greater and/or reduced risk for deterioration from repetitive soccer heading. In this proposed study we will investigate trait biomarkers hypothesized to have an association with neurodegenerative processes subsequent to brain injury. Specifically, we will examine the effect-modifying role of the Apolipoprotein E, Cholesterol Esterase Transfer Protein and Brain Derived Neurotrophic Factor polymorphisms. Furthermore, we will explore the extent to which the ex-vivo inflammatory stress response can explain the heterogeneity in outcomes. Under the mentorship of Dr. Michael Lipton and investigators with varying expertise pertaining to the project, I am confident that I will accomplish my goal of identifying biomarkers that confer greater vulnerability to heading related impairments. Furthermore, I will receive excellent training in clinical research methods and basic science techniques alike, which will serve as an excellent foundation for my ultimate goal of becoming an independent clinical Investigator.